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Carcinoma ex pleomorphic adenoma of the upper lip
Int. J. Oral Maxillofac. Surg. 2012; 41: 364–367 doi:10.1016/j.ijom.2011.12.008, available online at http://www.sciencedirect.com
Case Report Head and Neck Oncology
Carcinoma ex pleomorphic adenoma of the upper lip
D. Dyalram1, T. Huebner2, J. C. Papadimitriou2, J. Lubek1 1 Department of Oral & Maxillofacial Surgery, University of Maryland, Baltimore, MD, USA; 2 Department of Pathology, University of Maryland, Baltimore, MD, USA
D. Dyalram, T. Huebner, J. C. Papadimitriou, J. Lubek: Carcinoma ex pleomorphic adenoma of the upper lip. Int. J. Oral Maxillofac. Surg. 2012; 41: 364–367. # 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Carcinoma ex pleomorphic adenoma (CXPA) is a rare salivary gland malignancy most often reported within the parotid gland. Of the salivary gland tumours that occur within the minor salivary glands at least 50% are reported to be malignant. This proves to be inaccurate when describing salivary gland tumours within the upper lip which are usually benign. A Medline search of the English language literature yields only one case report of a CXPA located within the upper lip. The authors present a second case report of CXPA within the upper lip and a review of its pathologic features and management.
Salivary gland tumours account for approximately 3% of all head and neck tumours. Of tumours arising within the minor salivary glands, pleomorphic adenoma is considered to be the most common benign variant. It typically presents as a slow growing, painless mass located on the palate. There is a 2–4% malignant transformation rate in tumours that are long standing, most occurring within the parotid gland6. In a series of 380 intra-oral minor salivary gland tumours only 1.3% of malignant cases and 0.5% of all salivary gland tumours reported were carcinoma ex-pleomorphic adenoma (CXPA)2. In case reports, CXPA within the oral cavity is most often located within the palate. A medline search of the English language literature using mesh terms carcinoma ex-pleomorphic adenoma, upper lip and minor salivary gland yield only one case report9. The authors report a new case involving CXPA of the upper lip. 0901-5027/030364 + 04 $36.00/0
Case report
A 72-year-old African American male presented to the Oral & Maxillofacial Surgery service with a history of a painless lump in the labial sulcus of the left upper lip. The patient reported the lesion had been present for approximately 5 years. The mass had grown slowly over time and was now preventing the proper fit of his maxillary denture. No other symptoms were reported. The patient’s medical history included hypertension, type II diabetes mellitus and hypercholesterolemia, all of which were medically controlled. On clinical examination, the mass was 2 cm 2 cm with intact overlying mucosa within the labial mucosa of the left upper lip (Fig. 1). There was no palpable cervical lymphadenopathy. An MRI scan of the head and neck showed a well demarcated 2.2 cm 2.4 cm mass with high intensity signal on T2 imaging localized in the left upper lip (Fig. 2).
Accepted for publication 1 December 2011 Available online 29 December 2011
Pathologic diagnosis, established with an incisional biopsy performed under local anaesthesia, demonstrated a pleomorphic adenoma. The patient agreed to excision of the salivary gland tumour and local flap reconstruction. Intra-operatively the overlying mucosa was also excised with an extracapsular dissection of the salivary gland tumour. The defect was closed with local rotational advancement flaps. Final pathology reported a completely excised tumour with regions indicating malignant transformation including perineural invasion within the capsule, consistent with CXPA. The multidisciplinary Head & Neck tumour board decided that no adjuvant therapy was necessary since the tumour was in a location amenable to easy observation and had been completely excised with clear margins without evidence of extra-capsular extension. The patient has had no evidence of disease recurrence for the past 8 months.
# 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Carcinoma ex pleomorphic adenoma of the upper lip
365
Histology
Fig. 1. Raised mass in the labial mucosa of the upper lip measuring approximately 2 cm 2 cm.
Grossly, the specimen consisted of a 2.4 cm 2.1 cm 1.5 cm, firm, whitetan, focally haemorrhagic mass that appeared to abut the inked margins. The mass was homogeneous and well-circumscribed. Histologically the tumour was composed of nests and sheets of epitheloid cells with abundant light pink cytoplasm and round to oval nuclei with fine chromatin and inconspicuous nucleoli. The nests and sheets were separated by thin bands of fibrous stroma containing small capillaries. Additionally, small islands of cartilaginous and myxoid matrix were present within the tumour. Rare mitotic figures were present (up to 2 per high power field). Myoepithelial cells with vacuolated cytoplasm and smaller, dark round nuclei were also present in small numbers throughout the tumour. There were also areas containing scant amounts of myxoid type stroma and cells. The periphery of the tumour showed several small foci of perineural invasion, with tumour cells similar to those described above, invading and surrounding small nerve fibres. There was no evidence of extra-capsular extension. Immunohistochemical stains (S-100, Vantana, clone 4C4.9, lot number 812854, pre-diluted; Ki-67, Vantana, clone 30-9, lot number 1302558, pre-diluted; p63, Vantana, clone 4A4, lot number 1302558, pre-diluted; Actin, Vantana, clone HUC1-1, lot number 24108, pre-diluted; all immunostains performed on the Vantana Benchmark XT Autostainer) showed, as expected positive S-100 staining both in the epithelial cells as well as in the small nerves. Ki-67 was positive in less than 5% of the epitheloid cells. Actin and p53 immunostains were mostly negative (Figs. 3 and 4). Discussion
Fig. 2. MRI T2 axial image with gadolinium demonstrating a well-defined tumour within the upper lip with high signal uptake as compared to the surrounding muscle.
Malignant transformation of pleomorphic adenoma is rare, accounting for 6% of all pleomorphic adenomas (range 2–23%) and 12% of all salivary malignancies (range 3–42%). The malignant transformation can be categorized into two separate entities: CXPA and the extremely rare carcinosarcoma, composed of both carcinomatous and sarcomatous elements (50– 60 cases reported). Malignant transformation seems to have both a time and size dependent relationship6. There is a 2% chance of malignant changes in tumours less than 5 years old; this increases to 9% for tumours more than 15 years old8. A third variant includes the metastasizing
366
Dyalram et al.
Fig. 3. Low power, haematoxylin–eosin (H–E) stain of the salivary gland tumour showing encapsulation of the main tumour mass (arrows) as well as adjacent benign salivary gland, fibrous tissue and overlying squamous mucosa (arrow heads). The previous biopsy site is also evident (open arrowheads). The microscopic foci of perineural invasion at the periphery of the tumour are not appreciated at this magnification.
pleomorphic adenoma in which histologically benign pleormorphic adenoma spreads to distant sites. CXPA can display an array of different malignant epithelial cell types, the most common being poorly differentiated carcinoma, high-grade adenocarcinoma, and salivary duct carcinoma. Remnants of a benign mixed tumour may be present, but the diagnosis may also be made on the basis of a preexisting pleomorphic
adenoma in the clinical history. Often the mixed tumour component is quite small and the variability in the carcinomatous portion can account for the difficulty in establishing a diagnosis of CXPA. When present, perineural and lymphovascular invasion in an otherwise benign appearing tumour may signify focal malignant transformation6,7,10. Whilst there are no agreed histopathologic criteria, other features that suggest malignant
transformation in an otherwise benign tumour include infiltrative or destructive growth pattern, atypical nuclear changes, increased mitoses, necrosis, haemorrhage, dystrophic calcification, and local or distant metastasis6,7. The case presented here demonstrated both rare atypical cells within an otherwise pleomorphic adenoma histology combined with intracapsular perineural invasion. Management and prognosis of CXPA depends on the extent of capsular invasion. Tumours classified as non-invasive or minimally invasive (1.5 mm of invasion from the malignant component into the extra-capsular tissue) have a better prognosis, whilst invasive tumours (>1.5 mm of invasion into the extra-capsular tissue have a poor prognosis). Prognostic data are based on small case series with tumours most commonly located within the parotid and submandibular glands3,4,10. MRI is useful to help delineate the tumour from surrounding normal tissue. Small lesions are often homogeneous with well defined margins. MR T2 weighted images with their high signal intensity can best delineate tumour from the surrounding tissue whilst MRI T1 post contrast can help to identify possible perineural invasion. Ill-defined margins can help to establish the diagnosis of malignant degeneration of these mixed tumours11. Treatment of CXPA requires resection with appropriate margins. Most series
Fig. 4. (A) H–E (400 magnification) showing peripheral focus of perineural invasion; (B) S-100 immunostained section (400 magnification) showing tumour cells and nerve staining positively; (C) Ki-67 immunostained section (100 magnification) showing approximately 5% positivity in tumour cells, indicating a low proliferation index; (D) actin immunostained section (400 magnification) showing no staining in tumour cells; (E) p63 immunostained section (400 magnification) showing no staining in tumour cells.
Carcinoma ex pleomorphic adenoma of the upper lip demonstrate improved locoregional control and survival with completely excised margins. This is also demonstrated in the treatment of other malignant minor salivary gland tumours. CXPA of the major salivary glands has been noted to behave aggressively with high risk of nerve involvement (32%) and lymph node metastases (52%). The risk of regional metastases involving the minor salivary glands is much lower with CXPA and other more common malignant variants (mucoepidermoid, adenocarcinoma and adenoid cystic carcinoma)3,4,10. Pathologic factors such as tumour grade and extent of malignant component (>50% carcinoma) adversely affect survival. OLSEN et al. reported 63% of patients with high-grade carcinoma who died of the disease compared with those with tumours of lower grade histology10. Postoperative radiotherapy of CXPA is reserved for cases that show high grade histology, large size, bone invasion, cervical lymph node metastasis, positive margins or perineural invasion of named nerves. There are no standard chemotherapeutic treatments for salivary gland carcinomas10. Most involve case reports or phase II trials. A case report by Elad et al. describes the successful use of trastuzumab and capecitabine to treat metastatic recurrent CXPA5. As previously described locoregional recurrence and distant metastasis is highly dependent on the aggressiveness of the disease as demonstrated by the histologic grade, amount of carcinoma present within the tumour and depth of extracapsular extension. Approximately 50% of patients develop recurrence and up to 70% of patients develop local or distant metastases involving the lung or bone1,6,10. In the present case report involving a CXPA of the upper lip, the focus of carcinoma was contained within the completely excised pleomorphic adenoma. Favourable pathology was reported with negative surgical margins obtained, without evidence of capsular invasion or peri-
neural invasion of a named nerve. Based on the pathology report and limited literature on the prognosis and behaviour of CXPA, the multidisciplinary tumour board recommended close observation without further adjuvant treatment. The U.S. National Comprehensive Cancer guidelines (NCCN) were used to assist with a follow-up protocol and will include surveillance examinations every 2 months for the first 2 years. Surveillance imaging included an initial baseline post-surgical MRI with a repeat MRI at the 6-month follow-up and annually thereafter. CXPA is a rare but aggressive malignant salivary gland tumour most often occurring in the parotid gland. There is minimal information about the behaviour of this carcinoma regarding the involvement of intra-oral minor salivary glands. This is further complicated by the fact that less than 10% of salivary gland tumours located in the upper lip, are malignant2,6. Thus, one can conclude that the best prevention and management is to advise patients to undergo early and complete surgical treatment of the benign pleomorphic adenoma. Funding
3.
4.
5.
6.
7.
8.
9.
None. Competing interests
10.
None declared. 11.
Ethical approval
Not required. IRB exemption status. References 1. Akan H, Yildiz L, Unal R. Carcinoma ex pleomorphic adenoma of the minor salivary gland with pulmonary metastasis. Diagn Interv Radiol 2008;14:3–5. 2. Buchner A, Merrell PW, Carpenter WM. Relative frequency of intra-oral minor salivary gland tumors a study of 380 cases from
367
northern California and comparison to reports from other parts of the world. J Oral Pathol Med 2007;36:207–14. Carrillo JF, Maldonado F, Carillo LC, Ramirez Ortega MC, Gomez Pizano JG, Melo C, Chanona JG, Luna Ortiz K, Onate Ocana LF. Prognostic factors in patients with minor salivary gland carcinoma of the oral cavity and oropharynx. Head Neck 2011;33:1406–12. Copelli C, Bianchi B, Ferrari S, Ferri ES. Malignant tumors of intraoral minor salivary glands. Oral Oncol 2008;44:658–63. Elad S, Kelly RJ, Szabo E. Sustained response of carcinoma ex pleomorphic adenoma treated with trastuzumab and capecitabine. Head Neck Oncol 2010;2:12. Gnepp DR, Brandwein-Gensler MS, El-Naggar AK, Nagao T. Carcinoma ex pleomorphic adenoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. WHO classification of tumors pathology and genetics of head and neck tumors. Lyon: IARC Press; 2005. p. 242–4. Gnepp DR, Wenig BM. Malignant mixed tumors. In: Ellis G, Anclair P, Gnepp D, editors. Surgical pathology of the salivary glands. Philadelphia: Saunders; 1991. p. 350–68. Johns M, Goldsmith M. Incidence, diagnosis, and classification of salivary gland tumors. Oncology 1989:47–56. McNamara ZJ, Batstone M, Farah CS. Carcinoma ex pleomorphic adenoma in a minor salivary gland of the upper lip. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:e51–3. Olsen KD, Lewis JE. Carcinoma ex-pleomorphic: a clinicopathologic review. Head Neck 2001;23:705–12. Wiggins RH. Minor salivary gland malignancy, oral. In: Harnsberger HR, editor. , et al. editors. Diagnostic imaging head and neck. Salt Lake City: Amirsys; 2006.
Address: Joshua Lubek Department of Oral & Maxillofacial Surgery University of Maryland Baltimore MD USA Tel.: +1 410 706 7060 E-mail: [email protected]
Case Report Head and Neck Oncology
Carcinoma ex pleomorphic adenoma of the upper lip
D. Dyalram1, T. Huebner2, J. C. Papadimitriou2, J. Lubek1 1 Department of Oral & Maxillofacial Surgery, University of Maryland, Baltimore, MD, USA; 2 Department of Pathology, University of Maryland, Baltimore, MD, USA
D. Dyalram, T. Huebner, J. C. Papadimitriou, J. Lubek: Carcinoma ex pleomorphic adenoma of the upper lip. Int. J. Oral Maxillofac. Surg. 2012; 41: 364–367. # 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Carcinoma ex pleomorphic adenoma (CXPA) is a rare salivary gland malignancy most often reported within the parotid gland. Of the salivary gland tumours that occur within the minor salivary glands at least 50% are reported to be malignant. This proves to be inaccurate when describing salivary gland tumours within the upper lip which are usually benign. A Medline search of the English language literature yields only one case report of a CXPA located within the upper lip. The authors present a second case report of CXPA within the upper lip and a review of its pathologic features and management.
Salivary gland tumours account for approximately 3% of all head and neck tumours. Of tumours arising within the minor salivary glands, pleomorphic adenoma is considered to be the most common benign variant. It typically presents as a slow growing, painless mass located on the palate. There is a 2–4% malignant transformation rate in tumours that are long standing, most occurring within the parotid gland6. In a series of 380 intra-oral minor salivary gland tumours only 1.3% of malignant cases and 0.5% of all salivary gland tumours reported were carcinoma ex-pleomorphic adenoma (CXPA)2. In case reports, CXPA within the oral cavity is most often located within the palate. A medline search of the English language literature using mesh terms carcinoma ex-pleomorphic adenoma, upper lip and minor salivary gland yield only one case report9. The authors report a new case involving CXPA of the upper lip. 0901-5027/030364 + 04 $36.00/0
Case report
A 72-year-old African American male presented to the Oral & Maxillofacial Surgery service with a history of a painless lump in the labial sulcus of the left upper lip. The patient reported the lesion had been present for approximately 5 years. The mass had grown slowly over time and was now preventing the proper fit of his maxillary denture. No other symptoms were reported. The patient’s medical history included hypertension, type II diabetes mellitus and hypercholesterolemia, all of which were medically controlled. On clinical examination, the mass was 2 cm 2 cm with intact overlying mucosa within the labial mucosa of the left upper lip (Fig. 1). There was no palpable cervical lymphadenopathy. An MRI scan of the head and neck showed a well demarcated 2.2 cm 2.4 cm mass with high intensity signal on T2 imaging localized in the left upper lip (Fig. 2).
Accepted for publication 1 December 2011 Available online 29 December 2011
Pathologic diagnosis, established with an incisional biopsy performed under local anaesthesia, demonstrated a pleomorphic adenoma. The patient agreed to excision of the salivary gland tumour and local flap reconstruction. Intra-operatively the overlying mucosa was also excised with an extracapsular dissection of the salivary gland tumour. The defect was closed with local rotational advancement flaps. Final pathology reported a completely excised tumour with regions indicating malignant transformation including perineural invasion within the capsule, consistent with CXPA. The multidisciplinary Head & Neck tumour board decided that no adjuvant therapy was necessary since the tumour was in a location amenable to easy observation and had been completely excised with clear margins without evidence of extra-capsular extension. The patient has had no evidence of disease recurrence for the past 8 months.
# 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Carcinoma ex pleomorphic adenoma of the upper lip
365
Histology
Fig. 1. Raised mass in the labial mucosa of the upper lip measuring approximately 2 cm 2 cm.
Grossly, the specimen consisted of a 2.4 cm 2.1 cm 1.5 cm, firm, whitetan, focally haemorrhagic mass that appeared to abut the inked margins. The mass was homogeneous and well-circumscribed. Histologically the tumour was composed of nests and sheets of epitheloid cells with abundant light pink cytoplasm and round to oval nuclei with fine chromatin and inconspicuous nucleoli. The nests and sheets were separated by thin bands of fibrous stroma containing small capillaries. Additionally, small islands of cartilaginous and myxoid matrix were present within the tumour. Rare mitotic figures were present (up to 2 per high power field). Myoepithelial cells with vacuolated cytoplasm and smaller, dark round nuclei were also present in small numbers throughout the tumour. There were also areas containing scant amounts of myxoid type stroma and cells. The periphery of the tumour showed several small foci of perineural invasion, with tumour cells similar to those described above, invading and surrounding small nerve fibres. There was no evidence of extra-capsular extension. Immunohistochemical stains (S-100, Vantana, clone 4C4.9, lot number 812854, pre-diluted; Ki-67, Vantana, clone 30-9, lot number 1302558, pre-diluted; p63, Vantana, clone 4A4, lot number 1302558, pre-diluted; Actin, Vantana, clone HUC1-1, lot number 24108, pre-diluted; all immunostains performed on the Vantana Benchmark XT Autostainer) showed, as expected positive S-100 staining both in the epithelial cells as well as in the small nerves. Ki-67 was positive in less than 5% of the epitheloid cells. Actin and p53 immunostains were mostly negative (Figs. 3 and 4). Discussion
Fig. 2. MRI T2 axial image with gadolinium demonstrating a well-defined tumour within the upper lip with high signal uptake as compared to the surrounding muscle.
Malignant transformation of pleomorphic adenoma is rare, accounting for 6% of all pleomorphic adenomas (range 2–23%) and 12% of all salivary malignancies (range 3–42%). The malignant transformation can be categorized into two separate entities: CXPA and the extremely rare carcinosarcoma, composed of both carcinomatous and sarcomatous elements (50– 60 cases reported). Malignant transformation seems to have both a time and size dependent relationship6. There is a 2% chance of malignant changes in tumours less than 5 years old; this increases to 9% for tumours more than 15 years old8. A third variant includes the metastasizing
366
Dyalram et al.
Fig. 3. Low power, haematoxylin–eosin (H–E) stain of the salivary gland tumour showing encapsulation of the main tumour mass (arrows) as well as adjacent benign salivary gland, fibrous tissue and overlying squamous mucosa (arrow heads). The previous biopsy site is also evident (open arrowheads). The microscopic foci of perineural invasion at the periphery of the tumour are not appreciated at this magnification.
pleomorphic adenoma in which histologically benign pleormorphic adenoma spreads to distant sites. CXPA can display an array of different malignant epithelial cell types, the most common being poorly differentiated carcinoma, high-grade adenocarcinoma, and salivary duct carcinoma. Remnants of a benign mixed tumour may be present, but the diagnosis may also be made on the basis of a preexisting pleomorphic
adenoma in the clinical history. Often the mixed tumour component is quite small and the variability in the carcinomatous portion can account for the difficulty in establishing a diagnosis of CXPA. When present, perineural and lymphovascular invasion in an otherwise benign appearing tumour may signify focal malignant transformation6,7,10. Whilst there are no agreed histopathologic criteria, other features that suggest malignant
transformation in an otherwise benign tumour include infiltrative or destructive growth pattern, atypical nuclear changes, increased mitoses, necrosis, haemorrhage, dystrophic calcification, and local or distant metastasis6,7. The case presented here demonstrated both rare atypical cells within an otherwise pleomorphic adenoma histology combined with intracapsular perineural invasion. Management and prognosis of CXPA depends on the extent of capsular invasion. Tumours classified as non-invasive or minimally invasive (1.5 mm of invasion from the malignant component into the extra-capsular tissue) have a better prognosis, whilst invasive tumours (>1.5 mm of invasion into the extra-capsular tissue have a poor prognosis). Prognostic data are based on small case series with tumours most commonly located within the parotid and submandibular glands3,4,10. MRI is useful to help delineate the tumour from surrounding normal tissue. Small lesions are often homogeneous with well defined margins. MR T2 weighted images with their high signal intensity can best delineate tumour from the surrounding tissue whilst MRI T1 post contrast can help to identify possible perineural invasion. Ill-defined margins can help to establish the diagnosis of malignant degeneration of these mixed tumours11. Treatment of CXPA requires resection with appropriate margins. Most series
Fig. 4. (A) H–E (400 magnification) showing peripheral focus of perineural invasion; (B) S-100 immunostained section (400 magnification) showing tumour cells and nerve staining positively; (C) Ki-67 immunostained section (100 magnification) showing approximately 5% positivity in tumour cells, indicating a low proliferation index; (D) actin immunostained section (400 magnification) showing no staining in tumour cells; (E) p63 immunostained section (400 magnification) showing no staining in tumour cells.
Carcinoma ex pleomorphic adenoma of the upper lip demonstrate improved locoregional control and survival with completely excised margins. This is also demonstrated in the treatment of other malignant minor salivary gland tumours. CXPA of the major salivary glands has been noted to behave aggressively with high risk of nerve involvement (32%) and lymph node metastases (52%). The risk of regional metastases involving the minor salivary glands is much lower with CXPA and other more common malignant variants (mucoepidermoid, adenocarcinoma and adenoid cystic carcinoma)3,4,10. Pathologic factors such as tumour grade and extent of malignant component (>50% carcinoma) adversely affect survival. OLSEN et al. reported 63% of patients with high-grade carcinoma who died of the disease compared with those with tumours of lower grade histology10. Postoperative radiotherapy of CXPA is reserved for cases that show high grade histology, large size, bone invasion, cervical lymph node metastasis, positive margins or perineural invasion of named nerves. There are no standard chemotherapeutic treatments for salivary gland carcinomas10. Most involve case reports or phase II trials. A case report by Elad et al. describes the successful use of trastuzumab and capecitabine to treat metastatic recurrent CXPA5. As previously described locoregional recurrence and distant metastasis is highly dependent on the aggressiveness of the disease as demonstrated by the histologic grade, amount of carcinoma present within the tumour and depth of extracapsular extension. Approximately 50% of patients develop recurrence and up to 70% of patients develop local or distant metastases involving the lung or bone1,6,10. In the present case report involving a CXPA of the upper lip, the focus of carcinoma was contained within the completely excised pleomorphic adenoma. Favourable pathology was reported with negative surgical margins obtained, without evidence of capsular invasion or peri-
neural invasion of a named nerve. Based on the pathology report and limited literature on the prognosis and behaviour of CXPA, the multidisciplinary tumour board recommended close observation without further adjuvant treatment. The U.S. National Comprehensive Cancer guidelines (NCCN) were used to assist with a follow-up protocol and will include surveillance examinations every 2 months for the first 2 years. Surveillance imaging included an initial baseline post-surgical MRI with a repeat MRI at the 6-month follow-up and annually thereafter. CXPA is a rare but aggressive malignant salivary gland tumour most often occurring in the parotid gland. There is minimal information about the behaviour of this carcinoma regarding the involvement of intra-oral minor salivary glands. This is further complicated by the fact that less than 10% of salivary gland tumours located in the upper lip, are malignant2,6. Thus, one can conclude that the best prevention and management is to advise patients to undergo early and complete surgical treatment of the benign pleomorphic adenoma. Funding
3.
4.
5.
6.
7.
8.
9.
None. Competing interests
10.
None declared. 11.
Ethical approval
Not required. IRB exemption status. References 1. Akan H, Yildiz L, Unal R. Carcinoma ex pleomorphic adenoma of the minor salivary gland with pulmonary metastasis. Diagn Interv Radiol 2008;14:3–5. 2. Buchner A, Merrell PW, Carpenter WM. Relative frequency of intra-oral minor salivary gland tumors a study of 380 cases from
367
northern California and comparison to reports from other parts of the world. J Oral Pathol Med 2007;36:207–14. Carrillo JF, Maldonado F, Carillo LC, Ramirez Ortega MC, Gomez Pizano JG, Melo C, Chanona JG, Luna Ortiz K, Onate Ocana LF. Prognostic factors in patients with minor salivary gland carcinoma of the oral cavity and oropharynx. Head Neck 2011;33:1406–12. Copelli C, Bianchi B, Ferrari S, Ferri ES. Malignant tumors of intraoral minor salivary glands. Oral Oncol 2008;44:658–63. Elad S, Kelly RJ, Szabo E. Sustained response of carcinoma ex pleomorphic adenoma treated with trastuzumab and capecitabine. Head Neck Oncol 2010;2:12. Gnepp DR, Brandwein-Gensler MS, El-Naggar AK, Nagao T. Carcinoma ex pleomorphic adenoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. WHO classification of tumors pathology and genetics of head and neck tumors. Lyon: IARC Press; 2005. p. 242–4. Gnepp DR, Wenig BM. Malignant mixed tumors. In: Ellis G, Anclair P, Gnepp D, editors. Surgical pathology of the salivary glands. Philadelphia: Saunders; 1991. p. 350–68. Johns M, Goldsmith M. Incidence, diagnosis, and classification of salivary gland tumors. Oncology 1989:47–56. McNamara ZJ, Batstone M, Farah CS. Carcinoma ex pleomorphic adenoma in a minor salivary gland of the upper lip. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:e51–3. Olsen KD, Lewis JE. Carcinoma ex-pleomorphic: a clinicopathologic review. Head Neck 2001;23:705–12. Wiggins RH. Minor salivary gland malignancy, oral. In: Harnsberger HR, editor. , et al. editors. Diagnostic imaging head and neck. Salt Lake City: Amirsys; 2006.
Address: Joshua Lubek Department of Oral & Maxillofacial Surgery University of Maryland Baltimore MD USA Tel.: +1 410 706 7060 E-mail: [email protected]